Abstract:

Organoids, derived from adult or pluripotent stem cells through invitro differentiation, can recapitulate the cellular diversity, spatial organization, and physiological functions of invivo organs or tissues. The development of organoids has facilitated progress in developmental biology, genetics, pathology, and others. As an emerging interdisciplinary field guided by engineering principles, synthetic biology aims to design, modify, and construct biological components and systems with certain specifically designed functions through engineering and modular approaches. The invitro construction of organoids currently faces several challenges, including high cost, significant heterogeneity, and low throughput, which become more prominent when building complex organoid models. As a burgeoning field in recent years, synthetic biology has excellent potential to expand its applications and research directions. The optimization strategy of organoid construction has become intricately intertwined with the principles of synthetic biology in recent years. Simultaneously, the advancement of synthetic biology and its associated methodologies has propelled the progression of organoid technology. This review provides an overview of the historical developments and current challenges of organoids and synthetic biology while exploring the disparities and interconnections among these fields regarding research concepts and methods. Particularly, we will provide an overview of current design strategies for optimizing organoids and explore the fundamental applications of synthetic biology strategies in this context. Furthermore, we will examine the emerging role of synthetic biology tools in enhancing spatiotemporal fate regulation, structural self-organization, and functional capabilities of organoids. Lastly, we will discuss how derivative research based on organoid platforms contributes to advancing synthetic biology investigations. Overall, this review aims to elucidate the profoundly synergistic and mutually beneficial relationship between the rapidly evolving field of synthetic biology and organoid technology. By delving deep into the interconnectedness of these two disciplines, our objective is to facilitate further exploration of their potential integration in future research endeavors. Additionally, we seek to unravel feasible application scenarios that can harness the combined power of these two fields to bring about potential advancements in biomedical and life science.

Key words: cell fate determination, CRISPR, organoid, organs-on-chip, synthetic biology

摘要：

类器官由成体干细胞或多能干细胞在体外分化而来，可以在细胞类型、空间结构及生理功能上实现对体内组织器官的模拟。类器官的构建及技术完善，推动了发育生物学、遗传学、病理毒理学等发展。合成生物学是一门多学科交叉的新兴学科，以工程学思想为指导，旨在通过工程化、模块化的方法设计、改造、构建生物元件、系统、功能等。近年来类器官构建的优化方案体现了与合成生物学契合的研究理念，而合成生物学的发展及相关方法的产生也为类器官技术的发展起到了推动作用。本文将概述类器官和合成生物学的发展历程与面对的挑战，探讨类器官优化过程中合成生物学策略的体现与新兴的合成生物学工具对于类器官在时空命运调控、结构自组织及功能形成等方面的优化作用，简述基于类器官模型的研究对于合成生物学发展的促进作用。总的来说，本文旨在阐述合成生物学与类器官构建及优化之间相辅相成、互相促进的关系，并进一步探讨合成生物学与类器官在未来结合应用的潜力。

关键词: 细胞命运决定, CRISPR, 类器官, 器官芯片, 合成生物学